Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76

Vadim Pivniouk, Erdyni Tsitsikov, Paul Swinton, Gary Rathbun, Frederick W. Alt, Raif S. Geha

Research output: Contribution to journalArticle

314 Scopus citations

Abstract

The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation, SLP-76- deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4+8+ thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCRβ locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalCell
Volume94
Issue number2
DOIs
StatePublished - Jul 24 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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